Int J Stomatol

Int J Stomatol ›› 2024, Vol. 51 ›› Issue (1): 36-44.doi: 10.7518/gjkq.2024006

• Oral Oncology • Previous Articles     Next Articles

Ferroptosis and its implication in oral diseases

Fu Yu(),He Wei,Huang Lan()   

  1. Dept. of Orthodontics, Stomatological Hospital of Chongqing Medical University & Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences & Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
  • Received:2023-04-23 Revised:2023-08-30 Online:2024-01-01 Published:2024-01-10
  • Contact: Lan Huang E-mail:2022120653@stu.cqmu.edu.cn;lanhuang@hospital.cqmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(82170989);Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX0794)

RichHTML

29

PDF (PC)

1054

Abstract:

Ferroptosis is a regulated, iron-dependent form of cell death driven by lipid peroxidation and plays an important role in a variety of diseases. It has been studied in cancer, ischemia/reperfusion injury diseases, and neurodegenerative diseases. As an important form of cell death, ferroptosis has received increasing attention in oral disease research. Some advances have been achieved in related studies. Ferroptosis has become an emerging therapeutic target for oral cancer and has been associated with many inflammatory injury diseases. As a chronic inflammatory disease, periodontitis may have some correlation with ferroptosis. This work reviews current findings on ferroptosis to provide a reference for the mechanism, diagnosis, and treatment of related oral diseases.

Key words: ferroptosis, oral disease, oral cancer, periodontitis, cancer therapy

CLC Number: 

  • R782.4

TrendMD: 

Tab 1

Researches of ferroptosis in OSCC targeted therapy"

干预/靶向基因OSCC细胞系/组织样本相关表现参考文献
鼠尾草酸、Nrf2/HO-1/xCT途径SCC9-DDP和 CAL27-DDP 细胞（顺铂抵抗细胞）用鼠尾草酸处理顺铂耐药的OSCC细胞会降低GSH水平，增加ROS和脂质过氧化水平；这种作用可被liproxstatin-1逆转[13]
奎诺司他（quisinostat）CAL-27和TCA-8113细胞细胞的线粒体缩小且萎缩，线粒体嵴减少甚至缺失，线粒体膜密度增加，细胞内ROS水平增加，GPX4下调[14]
大黄根酚（chrysophanol）FaDu和SAS细胞ROS积聚，GPX4水平降低[15]
非热等离子体（non-thermal plasma）SAS和Ca9-22细胞细胞内发生了脂质过氧化，细胞内ROS水平、线粒体内ROS水平升高；非热等离子体所致的癌细胞死亡可被事先应用的FAC所促进，并被DFO所抑制[16]
PDT加Ce6-ErastinCAL-27 细胞细胞内ROS过度积聚，氧浓度增加，SLC7A11表达受到抑制[17]
circFNDC3B、miR-520d-5p32份 OSCC 样本，CAL27 和SCC15细胞系通过shRNA沉默circFNDC3B可以抑制GPX4和SLC7A11的表达，增强OSCC细胞中的ROS、铁和Fe（Ⅱ）水平；CircFNDC3B敲除加强了Erastin诱导的对OSCC细胞的生长抑制作用[19]
EZH2、SLC7A11、MiR-125b-5p20份TSCC样本，SCC9和CAL27细胞系EZH2和SLC7A11过量表达抑制了Erastin诱导的TSCC细胞的铁死亡，伴丙二醛水平和Fe（Ⅱ）水平降低[20]
miR-34c-3p43份OSCC样本，SCC-25和CAL27细胞miR34c-3p过表达使细胞中的ROS、丙二醛、Fe（Ⅱ）水平上升，GSH和GPX4水平降低，且可被Fer-1抑制[21]
PER1OSCC，SCC15 和CAL27 细胞系过表达PER1，GPX4、SLC7A11和GSH水平降低，运铁蛋白受体、丙二醛、ROS和Fe（Ⅱ）水平升高，线粒体皱缩，膜密度增加，线粒体嵴减少；沉默PER1，GPX4、SLC7A11和GSH水平升高，运铁蛋白受体、丙二醛、ROS和Fe（Ⅱ）水平降低，线粒体无明显形态学改变[22]
IL-6/STAT3/xCT129份HNSCC样本，12份黏膜白斑病样本，HN4和CAL27细胞沉默xCT，细胞线粒体皱缩，线粒体嵴减少；细胞内Fe（Ⅱ）增多，脂质过氧化水平增加，GSH水平降低[23]
AEBP1CAL27，SCC15和CAR（顺铂耐药细胞）细胞系沉默AEBP1增强了由SSZ诱导的细胞内ROS、游离铁、丙二醛表达水平升高，FTH1、GPX4和SLC7A11表达水平降低，环氧合酶2表达水平升高[24]
1 Gao MH, Monian P, Pan QH, et al. Ferroptosis is an autophagic cell death process[J]. Cell Res, 2016, 26(9): 1021-1032.
2 Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072.
3 Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases[J]. Signal Transduct Target Ther, 2021, 6(1): 49.
4 Balachander K, Paramasivam A. Ferroptosis: an emerging therapeutic target for oral cancer[J]. Oral Oncol, 2022, 131: 105970.
5 Stockwell BR. Ferroptosis turns 10: emerging me-chanisms, physiological functions, and therapeutic applications[J]. Cell, 2022, 185(14): 2401-2421.
6 Tang DL, Chen X, Kang R, et al. Ferroptosis: molecular mechanisms and health implications[J]. Cell Res, 2021, 31(2): 107-125.
7 Magtanong L, Ko PJ, To M, et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state[J]. Cell Chem Biol, 2019, 26(3): 420-432.e9.
8 Zilka O, Shah R, Li B, et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death[J]. ACS Cent Sci, 2017, 3(3): 232-243.
9 Guo C, Wang T, Zheng W, et al. Intranasal defero-xamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer’s disease[J]. Neurobiol Aging, 2013, 34(2): 562-575.
10 Chen KX, Ma SY, Deng JW, et al. Ferroptosis: a new development trend in periodontitis[J]. Cells, 2022, 11(21): 3349.
11 Kwon HK, Kim JM, Shin SC, et al. The mechanism of submandibular gland dysfunction after menopause may be associated with the ferroptosis[J]. A-ging (Albany NY), 2020, 12(21): 21376-21390.
12 谢章弘, 华清泉. 铁死亡在头颈部鳞状细胞癌中的研究进展[J]. 肿瘤防治研究, 2022, 49(4): 282-287.
Xie ZH, Hua QQ. Research progress of ferroptosis in head and neck squamous cell carcinoma[J]. Cancer Res Prev Treat, 2022, 49(4): 282-287.
13 Han L, Li L, Wu G. Induction of ferroptosis by carnosic acid-mediated inactivation of Nrf2/HO-1 potentiates cisplatin responsiveness in OSCC cells[J]. Mol Cell Probes, 2022, 64: 101821.
14 Wang XH, Liu K, Gong HM, et al. Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis[J]. Toxicol Appl Pharmacol, 2021, 410: 115363.
15 Ya-Hsuan L, Valeria C, Chun-Yen H, et al. Promotion of ferroptosis in oral cancer cell lines by chrysophanol[J]. Curr Top Nutraceutical Res, 2020, 18(3): 273-276.
16 Sato K, Shi L, Ito F, et al. Non-thermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe( Ⅱ )-dependent manner[J]. J Clin Biochem Nutr, 2019, 65(1): 8-15.
17 Zhu T, Shi LL, Yu CY, et al. Ferroptosis promotes photodynamic therapy: supramolecular photosensitizer-inducer nanodrug for enhanced cancer treatment[J]. Theranostics, 2019, 9(11): 3293-3307.
18 Hsieh PL, Chao SC, Chu PM, et al. Regulation of ferroptosis by non-coding RNAs in head and neck cancers[J]. Int J Mol Sci, 2022, 23(6): 3142.
19 Yang J, Cao XH, Luan KF, et al. Circular RNA FNDC3B protects oral squamous cell carcinoma cells from ferroptosis and contributes to the malignant progression by regulating miR-520d-5p/SLC7A-11 axis[J]. Front Oncol, 2021, 11: 672724.
20 Yu Y, MohamedAl-Sharani H, Zhang B. EZH2-mediated SLC7A11 upregulation via miR-125b-5p represses ferroptosis of TSCC[J]. Oral Dis, 2023, 29(3): 880-891.
21 Sun K, Ren WH, Li SM, et al. MiR-34c-3p upregulates erastin-induced ferroptosis to inhibit proliferation in oral squamous cell carcinomas by targeting SLC7A11[J]. Pathol Res Pract, 2022, 231: 153778.
22 Yang YX, Tang H, Zheng JW, et al. The PER1/HIF-1alpha negative feedback loop promotes ferroptosis and inhibits tumor progression in oral squamous cell carcinoma[J]. Transl Oncol, 2022, 18: 101360.
23 Li MY, Jin SF, Zhang ZY, et al. Interleukin-6 facilitates tumor progression by inducing ferroptosis resistance in head and neck squamous cell carcinoma[J]. Cancer Lett, 2022, 527: 28-40.
24 Zhou QW, Wang XQ, Zhang YX, et al. Inhibition of AEBP1 predisposes cisplatin-resistant oral cancer cells to ferroptosis[J]. BMC Oral Health, 2022, 22(1): 478.
25 晏子钦, 魏明波, 程波. 基于铁死亡相关基因的口腔鳞状细胞癌的生物信息学分析[J]. 临床口腔医学杂志, 2022, 38(1): 19-22.
Yan ZQ, Wei MB, Cheng B. Bioinformatics analysis of oral squamous cell carcinoma based on the expression of ferroptosis-related genes[J]. J Clin Stomatol, 2022, 38(1): 19-22.
26 吴莹莹, 孙越, 邹燕梅, 等. 筛选影响口腔鳞状细胞癌预后的铁死亡相关lncRNAs并构建预后风险模型[J]. 临床口腔医学杂志, 2021, 37(9): 535-538.
Wu YY, Sun Y, Zou YM, et al. Screening ferroptosis-related lncRNAs that affect the prognosis of oral squamous cell carcinoma and constructing a prognostic risk model[J]. J Clin Stomatol, 2021, 37(9): 535-538.
27 Huang C, Zhan L. Network pharmacology identifies therapeutic targets and the mechanisms of glutat-hione action in ferroptosis occurring in oral cancer[J]. Front Pharmacol, 2022, 13: 851540.
28 Gu WC, Kim M, Wang L, et al. Multi-omics analys-is of ferroptosis regulation patterns and characterization of tumor microenvironment in patients with oral squamous cell carcinoma[J]. Int J Biol Sci, 2021, 17(13): 3476-3492.
29 Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and propo-sal of a new classification and case definition[J]. J Clin Periodontol, 2018, 45(): S149-S161.
30 Yao C, Lan DM, Li X, et al. Porphyromonas gingivalis is a risk factor for the development of nonalcoholic fatty liver disease via ferroptosis[J]. Microbes Infect, 2023, 25(1/2): 105040.
31 Liu SX, Butler CA, Ayton S, et al. Porphyromonas gingivalis and the pathogenesis of Alzheimer’s di-sease[J]. Crit Rev Microbiol, 2023: 1-11.
32 Qiao SW, Li BS, Cai Q, et al. Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo [J]. Oral Dis, 2023, 29(8): 3571-3582.
33 Bullon P, Cordero MD, Quiles JL, et al. Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis[J]. Free Radic Biol Med, 2011, 50(10): 1336-1343.
34 Yang WY, Meng X, Wang YR, et al. PRDX6 alle-viates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis[J]. Acta Odontol Scand, 2022, 80(7): 535-546.
35 Wang HW, Qiao XT, Zhang C, et al. Long non-coding RNA LINC00616 promotes ferroptosis of periodontal ligament stem cells via the microRNA-370/transferrin receptor axis[J]. Bioengineered, 2022, 13(5): 13070-13081.
36 Lu R, Meng H, Gao X, et al. Effect of non-surgical periodontal treatment on short chain fatty acid le-vels in gingival crevicular fluid of patients with ge-neralized aggressive periodontitis[J]. J Periodontal Res, 2014, 49(5): 574-583.
37 Zhao YH, Li J, Guo W, et al. Periodontitis-level butyrate-induced ferroptosis in periodontal ligament fibroblasts by activation of ferritinophagy[J]. Cell Death Discov, 2020, 6(1): 119.
38 Zhang CR, Xue PX, Ke JG, et al. Development of ferroptosis-associated ceRNA network in periodontitis[J]. Int Dent J, 2023, 73(2): 186-194.
39 Pan SY, Hu B, Sun JC, et al. Identification of cross-talk pathways and ferroptosis-related genes in pe-riodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation[J]. Front Immunol, 2022, 13: 1015491.
40 Leite-Lima F, Bastos VC, Vitório JG, et al. Unvei-ling metabolic changes in marsupialized odontoge-nic keratocyst: a pilot study[J]. Oral Dis, 2022, 28(8): 2219-2229.
41 Zhou H, Zhou YL, Mao JA, et al. NCOA4-mediated ferritinophagy is involved in ionizing radiation-induced ferroptosis of intestinal epithelial cells[J]. Redox Biol, 2022, 55: 102413.
[1] Luo Xiaojie,Wang Dexu,Chen Xiaotao. Relationship between periodontitis and ferroptosis based on bioinformatics analysis [J]. Int J Stomatol, 2023, 50(6): 661-668.
[2] Huang Yuanhong,Peng Xian,Zhou Xuedong.. Progress in research into the effect of Rhizoma Drynariae on the treatment of bone-related diseases in the oral cavity [J]. Int J Stomatol, 2023, 50(6): 679-685.
[3] Hu Jia,Wang Xiuqing,Lu Guoying,Huang Xiaojing.. Regenerative endodontic procedures for permanent tooth with immature apices in adult patients [J]. Int J Stomatol, 2023, 50(6): 686-695.
[4] Gong Meiling,Cheng Xingqun,Wu Hongkun.. Research progress on the correlation between Parkinson’s disease and periodontitis [J]. Int J Stomatol, 2023, 50(5): 587-593.
[5] Xu Zhibo,Meng Xiuping.. Research progress on mechanism of Enterococcus faecalis escaping host immune defense [J]. Int J Stomatol, 2023, 50(5): 613-617.
[6] Jiang Yueying,He Yutian,Li Ting,Zhou Ronghui.. Research progress on the application of near infrared fluorescence probe in the diagnosis of oral cancer [J]. Int J Stomatol, 2023, 50(4): 407-413.
[7] Fan Lin,Sun Jiang.. Application of microneedles in stomatology [J]. Int J Stomatol, 2023, 50(4): 472-478.
[8] Yang Qianjuan,Song Zhixin,Fang Shishu,Gu Zexu,Jin Zuolin,Liu Qian. New advances in oral diseases based on salivary metabolomics [J]. Int J Stomatol, 2023, 50(3): 321-328.
[9] Sun Jia,Han Ye,Hou Jianxia. Research progress on the role of interleukin-6-hepcidin signal axis in regulating the pathogenesis of periodontitis-associated anemia [J]. Int J Stomatol, 2023, 50(3): 329-334.
[10] Lin Huiping,Xu Ting,Lin Jun.. Research progress on artificial intelligence techniques in diagnosis of oral cancer and potentially malignant disorders [J]. Int J Stomatol, 2023, 50(2): 138-145.
[11] Liang Zhiying,Zhao Yuanxi,Zhu Jiani,Su Qin.. Retrospective analysis of clinical data of 288 cases of endodontic microsurgery on anterior teeth [J]. Int J Stomatol, 2023, 50(2): 166-171.
[12] Wang Taiping,Shi Xinglian,Li Zhezhen,Liu Mei,Jiang Jianhong. Analysis of psychological factors and intervention in patients with oral cancer [J]. Int J Stomatol, 2023, 50(2): 203-209.
[13] Chen Yifei,Zhang Binjing,Feng Shuqi,Xu Rui,Yang Shuxian,Li Yuqing. Effects of flavonoids on oral microorganisms and its mechanism [J]. Int J Stomatol, 2023, 50(2): 210-216.
[14] Liu Tiqian,Liang Xing,Liu Weiqing,Li Xiaohong,Zhu Rui.. Research progress on the role and mechanism of occlusal trauma in the development of periodontitis [J]. Int J Stomatol, 2023, 50(1): 19-24.
[15] Li Qiong,Yu Weixian. Research progress on resveratrol for the treatment of periodontitis and its bioavailability [J]. Int J Stomatol, 2023, 50(1): 25-31.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .